Fibroblast growth factor 21 (FGF21) plays a role in regulating adaptation to various metabolic abnormalities. In addition, FGF21 is involved in controlling glucose and lipid homeostasis. The regulation of FGF21 is a complex process and depends upon multiple metabolic factors and hormones. Humans and animals with obesity or type 2 diabetes have abnormal expression and changes of FGF21 in the circulation. Interventional studies in rodents and monkeys with obesity, insulin resistance or type 2 diabetes revealed a potential therapeutic relevance of FGF21 in correcting these abnormalities. This review summarizes the current knowledge about the regulation of FGF21 by distinct metabolic and endogenous factors, considering the most relevant studies. In this context, the results of interventional studies in humans and various animal models of diseases, such as diabetes and obesity, are discussed. In addition, potential mechanisms of the molecular regulation of FGF21 expression and secretion are reviewed.
Keywords: FGF21; adipose tissue; diabetes; glucagon; insulin resistance; liver; obesity.